This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Research in the Georgiadis lab is directed toward understanding the role of protein-nucleic acid interactions in such fundamental biological processes as replication, nuclear export, and regulation of gene expression. Our approach is to integrate X-ray crystallographic studies with complementary biochemical studies. Current research efforts are focused on understanding in atomic detail two critical steps in the retroviral life cycle: (1) replication of the retroviral genome by reverse transcriptase and (2) nuclear export of unspliced retroviral transcripts including the constitutive transport element (CTE). These studies are related more generally to (1) the understanding of nucleic acid interactions that are important during replication through comparative analysis with related polymerases and (2) nuclear export of mRNA, which is mediated by the same host factor, Tap. A related protein, Ape1 (Ape(delta)40) is a protein that participates in redox regulation of transcription factor function. The redox function of Ape1 involves reduction of oxidized cysteine residues within the DNA binding domains of several transcription factors, including c-Jun. E3330 is a small molecule containing a quinone. It binds directly to Ape1 and inhibits the redox function of Ape1. E3330 blocks the ability of Ape1 to reduce c-Jun.
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